HU229886B1 - Benzenesulfonyl cloride derivates suitable for the preparation of herbicidal n-(triazoloazinyl) benzenesulfonamid e compounds - Google Patents

Description

<Jazinil) · -benzcl

BACKGROUND OF THE INVENTION The present invention relates to benzenesulfonyl chloride derivatives useful in the preparation of herbicidal N - (N, N-triazoloazinyl-benzenesulfonamide compounds.

is an important aspect of modern agriculture and agriculture. While many compounds are known for controlling unwanted vegetation, there is still a need for new compounds that are generally more effective, more selective, less hazardous to crops, humans or the environment, more economical in their application, or otherwise beneficial

Many benzenesulfonamide derivatives are known and include herbicides. For example, U.S. Pat. No. 4,838,075 has a herbicidal action on M-

- ([1,2 _t 4] -tazol [1,5-a] pyrimidine n-2-B) benzenesulfonamide, U.S. Pat. No. 4,885,958. 1,2,4-triazolo [1,3,5] trlazl-n-2- (5-yl) benzenesulfonamide compounds are disclosed. Among the N-phenyl-ard-sulfonamide derivatives are also herbicidal compounds. For example, U.S. Pat. No. 5,183,995 discloses N- (substituted-phenyl) -Π, 2,4] -triazolo [1 _; 5 cjpirimidin szuifonamldokat-2, No. 5,571,755 US Patent államok111338-25ö8e v flat Cszubsztituált N ~ phenyl} ~ [1 ₁ 2,4] -tríszolo (1,0-a-S -oindio

We have found that a new N- (triazoloazole) arylsulfonamide chemical is a

N - ([1 _f 2,4J triazol ~ | 1 .S-cjplrimidin-S-yl-benzene-szolfonamidok,

N- (Í1,2,4] triazolo [1,5-cjpinmldin ~ 2 ~ yl ~ pyridin ~ szulfonamldok,

N - ([1,2,4] thiazole-1,5-a-pyridine n-Z-h-benzenesulfonate,

N - ([1,2 _t 4] -irazolo [1 H-aspirldin-Z-11-pyridylsulfonamides belong to effective herbicides and unwanted vegetation, either preemergent or preemergent). , which is also beneficial in its toxicological and environmental effects,

The present invention relates to the use of keywords in the preparation of the above compounds. The intermediate is of formula (III)

Ik where

A is OCH ₂ CF ₃ , OCH ₂ CHF _2, OCH ₂ CH ₂ F

OCH ₂ CH ₂ CF ₃ or ÖCH (CH ₂ F} ₂ ;

Casting B sign CF ₃ : and ö denote H,

Compounds which are preferred compounds of the invention

The compounds of the present invention have the following formula (H) - (tri-z-o-z-n-11) ~ -i-z-z-n-z (i)

and derivatives thereof for the preparation of salts thereof

X is a nitrogen atom or a group of formula C-Y; W is (C 1 -C 3) alkyl, chloro, bromo, fluoro or

Y is hydrogen, mephos, fluorine, chlorobromine or iodine, or methdosopoft optionally substituted with 1 to 3 fluorine atoms;

O (C 1-3 alkyl), hydrogen, fluoro, chloro, bromo or iodo is S (C 1-3 alkyl) or methyl optionally substituted with 1-3 fluoro, with the restriction wherein W and Z are represented by at least one O (C 1 -C 3) alkyl group,

Q is C-H or nitrogen:

A is fluorine, chlorine, bromine or iodine or -CO2 (C1-C4 alkyl); or C 1 -C 3 alk, O (C 1 -C 4 alkyl), O (C 3 -C 4 alkenyl), O (C 3 -C 4 alkynyl) or C 8 -C 3 alkyl, any of which is optionally substituted with 0, (C 1 -C 3) alkyl, S (C 1 -C 3) alkyl, chloro or bromo, or cyano or with as many fluorine atoms as possible or less; or 2-methylo-1,3-d benzo-2-yl; and when 0 is nitrogen, the presence of A may also be hydrogen;

B is hydrogen, fluoro, chloro, bromo or iodo, or nitro, cyano, -C0 (C1-C4 alkyl), NH (C1-C3 alkyl), or N (C1-C3) or (C 1 -C 4 alkyl), O (C 3 -C 4 alkenyl), O (C 3 -C 4 alkynyl) - (C 1 -C 3 alkyl), (C 1 -C 3 alkyl), (C 1 -C 3 alkyl), (C 1 -C 3 alkyl), alkyl) -. 80 (C 1-3 alkyl) -, S0s (C1-3 alkyl) -, 8 (C3-4alkenyl) -. 80 (C3-4alkenyl) - 8 O ₂ (3- 4 -alkenyl) -, 8 (C3-4-alkynyl) -, 80 (C3-4-alkynyl), or _SO2 (C3-4 alkinílj group, any of which is optionally substituted by making the maximum number or less fluorine atoms, with the proviso that if one of A and B is a bridge atom, the other is hydrogen;

D is hydrogen, fluorine, chlorine, b-or iodine, C 1-3 alkyl, meloxyl, ethoxy, fluoromethyl, difluoromethyl or al.

0-4 oxyfluoromethyl group, or B and D together an O-CH3-O group optionally substituted with one or two fluorine atoms or methyl groups;

T is hydrogen, SO ₂ R, C (O) R, or -CH ₂ CR ₂ C (O) OR, wherein

R is (1-4C) alkyl, (C3 -C4) alkenyl, alkynyl, any of which may be substituted with 2 chlorine or bromine atoms, 0 (C1-C4 alkyl) -carbonate or a maximum number of fluorine atoms or less; and R ^{f is} hydrogen, C 1 -C 4 alkyl, C 3 -C 4 alkenyl, or C 3 -C 4 alkenyl;

and when T is hydrogen, the agriculturally acceptable salts of the compounds.

Compounds in which X is either nitrogen or C-Y and those in which Q is either nitrogen or C-H are preferred compounds of the invention. Among the compounds preferred according to the invention there are many that contain a (W) methoxy group at the 5-position of the triazoloazinyl ring system and a (Z) methoxy group or a halogen atom at the 3-position. Some of the preferred compounds also have ortho-methoxy substituents (A is the filamentary moiety of the other ortho-heterocyclic substituent (.A or B) and are in the meta-position of (D) hydrogen; and preferred are brain ortho-methoxy substituents in combination with or a meta-position methyl or chloro substituent (0) if the other ortho substituent (8) is unsubstituted or a brain ortho-trifluoromethyl substituent (B) with a wide variety of other ortho substituent chemical substituents and g é η ne I kom fa ináéi óba n.

The term "agriculturally acceptable salts" refers to compounds in which the acid sulfonamide proton of the compound of formula (I) is replaced by a cation which is not harmful to the crop being treated, is not harmful to the user, the environment or the end user of the treated crop. alkali metals and alkaline earth metals, and from the ammonium or magnesium cation and

R ^S R ⁷ R ⁸ NH sm independently represents 3 to 12 carbon atoms

«9 atoms are sodium to the hydroxy group of C1-C8, the element al bum,

R '\ R' and hydrogen or C 1 -C 12 alkyl having 3 to 12 carbon atoms, any of which may be optionally substituted with one or more C 1 -C 1 -C 8 alkylthio, with the proviso that

uhh: z outside

Two of R, R 'and R can be digested, which has 1 to 12 carbon atoms and up to two

glaze. Salts of compounds of Formula I are contemplated to form compounds of Formula I wherein T is hydrogen with a metal hydroxide such as sodium hydroxide, lumium hydroxide or magnesium hydroxide or an amine with roxyl 11, pe For example, ammonium chloride, dlyallylamine, 2-butoxyethylamine, morpholine

Reaction with amine or fenzyl · amine.

Table 1 shows the compounds of the formula (I) which have been used in the abdomen II of this invention.

spreadsheet

V «gyöí <n number X w z T She. THE 3 s AÚfcj » sa from cico-iSCisSias / Dryfire. 3 «IAU %! C SOS w «3 FTI OCH C! s ............. C8 OCWiC "sF c - K # .YC <k POF 238 240 38.5 35.5 $ 2.1 2.30 15.0 14.8 40 ! 4 · OCX ci rí <; Ik ^ íXZRj CF * M yellowish- fests fx. "· 202 3 »S 35. S ski ;,? 2.26 1.54 13.3 22.1 : 26? fiction OCS-i-s c <; « ₃ >! t%: OCR;! C «j.? 0 = 5 H powder 333- 235 42.3 41.4 3.23 3.66 35.2 14.3 : iss- Iá OC -:!, Octo K CH GCHiCe C? 5 M Bi-nsr saiíáro the core m '213 38.3 38.3 1.61 $ 2.5 14.0 13/3 I AM? N OCMs 8 OH Uf7 "~ 8 síüáf-p ' aw 233- 232 Λ04 40.6 3:24 3U2 24.1 34.0 ISS s ÖCfe O <.>, W. ch OCH-CfoCFs c? - H Fe? S sitire e "ysg 211-231 57.0 2.30 2.23 12.7 12Λ ISO N <> CV \ OCM, POI <8 lot BEAT" 8 yellowish ms srbani material 22V 224 33Λ 2:53 2/74 24.5 .14,3 2 OS N oesV H :;>! OCS ijCM; " K yellowing of young 3 srtSáre. stoág ...... 330- 223 38.6 33.3 3:03 2, S6 28.0 í? .3 330 N ock.s; OCH CÓCOj ScHiCíÚ? PGI 8 yellowish- in · - »» powder 232 226 42.6 42.2 3.38: 3-33 ; 23.6; 13.0 23 » FCI CX3O OCVx Söjíto CH ÖCttaCKzF Ci ^: i H 237 ÍXÍHj coc% CH OCtoCHsF Cf = _s H Z = t & N _¥ COI OCMs C10-CH2 · OC5 < ₅ £ H Ix ^ SCF IIS 8

Compounds of formula (I) wherein Α Ϊ is hydrogen may be prepared by reacting a triazole of formula (Π) with an benzene sulfonyl chloride of formula (III) or a pindin-3-sulfone H-clone. In formula (W), W, Z and X are as defined in formula (I). The two compounds are present in substantially the same molar amount in polar aprotic solvents such as acetonitrile, pyridine and catalytic amount (the sulfonyl chloride derivative 5-25). mole%) in the presence of dimethylsulfoxysd at room temperature. If necessary, additional sulfonyl chloride derivatives such as pyridine and dimethyl sulfoxide may be added to the reaction mixture to complete the reaction. The reaction may take from several hours to several days.

Dry nitrogen shielding gas may be used to exclude moisture. The resulting compounds of formula (I) are solid, poorly soluble in water and in a number of standard organic solvents, and can be recovered from the reaction mixture by conventional means.

The formula sulfonyl chloride derivative, and (H) for preparing a 2-amino- (1,2 ~ _t 4jtnazGloazin derivative reaction can advantageously be carried out using the 2-amino- [1,2,4jtrlazoloazin derivative (III) firstly the formula (IV) is converted to the N Ars Iout l szlll derivative I, where W, X and 2 is as defined above in (I) to formula and R is ^t! 1-4C alkyl. Typically, the N-írimetH- silH and ΜΜΗΙΗΙΙΙΙ ΖΖΖΖΖΖ Ez Ez Ez EzΖό EzΙ módszer módszer hasonló hasonló hasonló hasonló módszer módszer módszer módszer hasonló módszer módszer hasonló módszer módszer hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló hasonló and to make it easier,

The 2-amino- [1,2,4] thiazoloazine derivative of formula (H) can be converted into the M-trialkylsilyl derivative of formula (IV) by first adding a chloro-trialkH-sNane to sodium hydroxide. or cabum iodide in a solvent such as aoethonitrile under anhydrous conditions, and to this mixture is added the 2-8msno- [1,2,4] trlazolazazine derivative and a trialkylamine such as trietbamine, typically at room temperature, with stirring. -trialkylsilane and 3 ~ amlno ~

The [1,2,4] trlazoloazoline derivative is generally used in an amount close to equivalents. The reaction time may vary from a few hours to a day depending on the fattyalkylamine used and the 2-aminol, 2,4) thiazoloazole derivative. The reaction mixture is then diluted with a non-polar solvent such as ether or t-2-dichloroethane, the insoluble salts are removed by filtration and the volatile components are evaporated under reduced pressure. The resulting tetraalkyl derivatives of formula (IV) are recovered and, since they are unstable in the presence of water, are kept dry.

The compound of formula (IV) prepared as above or otherwise can then be condensed without further purification or after purification, the condensation of the Sutenyl Clonde derivative of formula (IN) can generally be carried out in a solvent, e.g. in acetonitrile, treated with equimolar amounts of pyridine or mephylpyridine beige, and nearly equimolar amounts of fluoride ions such as cesium fluoride or tetraalkylammonium fluoride, which facilitate the reaction, and catalytic amounts (3-20% of the sulfonyl clonde derivative) ) in the presence of dimethylsulfoxide. The condensation is typically carried out at 1080 ° C in anhydrous conditions, usually for 2 to 18 hours. The N- (triazolazazinyl) arylsulfonamides of general formula (I) are then removed from the solids with water-soluble salts and / or soluble organic substances by means of an extraction agent, using conventional syllables.

Compounds of formula (I) wherein T is a non-hydrogen substituent can be prepared by acylation of the corresponding compounds of formula (I) wherein T is a hydrogen atom, for similar sulfonamides under acylation conditions known in the art. Examples of suitable acylating agents include alkanoyl chlorides (e.g., proplonyl chloride or trifluoroacetyl chloride), chloroformates (e.g., 2-mefloxyl-1 H-chloroformate)] _and carbamoyl moiety.

-chlorlds (e.g., Η ',- ^: -0ΐ3ΐΙΠ-Κ3ί · ό3ηιοΐΰΑ1θΓ! és) and azaikyl i z ο I a π (k e d d i u u 2 - k 11 - 1 11 o ol ao á t),

A compound of formula (I) wherein W is chloro, with an appropriately selected nucleofd reagent, known in the art, by substituting W for fluoro, bromo or O (C 1-3 alkyl) or S (C 1-3 alkyl) osoporfof. The chloro substituent (W) at position 5 is generally more easily substituted, such as at position 6 (X-CY) or position 8 (Z), so that the substitution reaction can be carried out selectively. .

A number of general formula (11) having X in the group C-Y; The ethyl 2-amino [1,2,4] quinazolo [1,5-a] pyridine derivative can be prepared by reaction of N- (2-pyridinyl) -N'-carbethoxy-thiourea (V) with hydroxylamine. The reaction is usually quenched in a solvent, such as ethanol and air. Typically, hydroxylamine is prepared by the neuralization of its tail to diisopropyl ethylene; for this purpose, a spherically inhibited ferric amine or an alkali metal alkoxide such as sodium ethoxide is used. The obtained general formula (II) is recovered by conventional methods, for example by evaporation of the volatile components from the reaction mixture, and by known methods, for example, into water; and / or other solvents which do not dissolve the product are extracted and purified. The starting h1- (2-pyridineH) -H'-carbefoxylthiocarbamide of formula (V) is prepared by reaction of the appropriately substituted Z-aminopyrldine derivative with efoxAcarbonyl isothioanate. The reaction is usually carried out in the presence of an organic solvent at room temperature. The complete process is described in U.S. Patent No. 5,571,775.

The starting substituted 2-aminopyridine derivatives are known and may be prepared as described herein or as known in the art.

Compounds of formula II wherein X is C-Y may also be prepared from the appropriately substituted 2-cyanoaminopyridine derivatives by the method of B. Vercek et al., Menatshefte für Chemie, 114: 739-738 (1983). The preparation of these endings is also possible by the method of K. T. Potís et al., J. Org. Chem. 31, 265-273 (1966).

X is nitrogen of formula (I)

The 2-amino- [1,2: 4] triazolo [1,5-G] pyrimidine derivatives can be prepared from the 4-hydrazinopyrimidine derivatives of formula VI. In formula (VI), W represents a mefyl group, a hydrogen or chlorine atom, and Z represents a hydrogen or halogen atom, a fatty xyl group or an alkylthio group. The compound of formula (VI) is first treated with cyanogen chloride. In the reaction, the 3-amino-η-p-8-substituent of formula (VII) is converted to 1,2-substituent of 1,2, 4] tr I is the hydrobromide of - ο I o (4,3 - c] ρ 1 rimidium in formula (VII) W is methylthio, hydrogen or chlorine, and Z is hydrogen or halogen , represents an alkoxy or alkylthio group. The reaction is usually carried out in an organic solvent such as isopropanol at room temperature. The reaction product is obtained by conventional methods such as adding a non-polar solvent such as diethyl ether to the reaction mixture and filtering off the precipitated solid. The above intermediate containing AW is methylthio and the desired W is alkoxy (II). The compound may be converted to the compound by treating the methylthio derivative with an alkali metal alcoholate such as sodium methylate or potassium ethylate and ethyl acrylate in the presence of the appropriate alcohol as a solvent. During the rearrangement, the methylthio group is replaced by an alkoxy group from the alcohol in the medium. The reaction is usually carried out at a temperature below 25 ° C. To obtain the desired compound (II), the reaction mixture is neutralized with acetic acid and the precipitated solid is filtered off. or by any other conventional method,

The compounds of formula (II) wherein X is nitrogen and W is hydrogen or chlorine are

It can also be prepared by re-isomerization of the intermediate [4,3-c] containing a hydrogen or chlorine atom with triacylamine base. The starting material for these processes of formula (VI) (4-hydrazinopyrimidine derivative) can be prepared from hydrazine derivatives of 4-chloropyrmid derivatives well known in the art.

Compounds of formula (II) wherein X is nitrogen are prepared according to the method of G. W. fvbller et al. Chem.

Sec., 1965, 3357 and 5842 (1963)].

Also included are compounds of formula II wherein X is nitrogen. Thus, the present invention also relates to 2-amino [1,2,4] triazolo [1,5-c] pyrimidine derivatives of the general formula (Na) wherein W is (C1-C3) alkyl, chloro, bromo, fluorine or hydrogen: Z represents O (C1-C3 alkyl), hydrogen, fluoro, chlorine, bromine or iodine S (C1-C3 alkyl) or methyl optionally substituted with 13 fluoro atoms, with the proviso that at least one of W and Z is O (C 1 -C 3) alkoxy. Compounds of this type wherein one of W and 2 is methoxy and the other is fluorine, chlorine or bromine are methyl, , methoxy or ethoxy, are often preferred, those wherein W is methoxy and 2 are methoxy, fluoro, chloro or bromo are often more preferred.

Substituted benzene sulfonyl chloride (Uh) can be prepared by the methods described herein or by methods known in the art, either general or specific. Many compounds, such as 2-methoxy-6- (fluorophenyl) benzene

-SU glaze can be prepared by reacting the corresponding benzene derivative with 3-trifluoromethylanisole with butyl lithium and converting the resulting phenyl lithium into the corresponding propyl thio compound and then reacting it with chlorine. methods are generally used. Many pro-pH or benzH-thiophenol derivatives can be prepared by standard methods of reaction of the corresponding thiophenol derivative under reaction conditions;

oxidized with chlorine. The fend. which wood maztath the capital can be directly transformed with sulfur dioxide or sulfur dioxide I am in sign of η I sulfur ο η i I -chloride I d - derivative of hN'- tetrametH en. Other sulfonyl chloride derivatives such as 2- (1,1,2,2-trifluoromethoxy) benzenesulfonyl chloride may be prepared by the presence of the corresponding aniline or 3-aminopyridine derivative and concentrated aqueous hydrochloric acid sulfonyl. chloride derivatives such as

2-methoxy-o-r

ZOl-SUIK di · can also be produced by direct chlorosulfonation of our benzene

The N- (1-imidazolazinyl) -beta-derivatives of formula (I) may be used directly as berries, but preferably in an herbicidal effective amount of the compound with at least one agriculturally acceptable adjuvant or carrier.

Examples 1-22 below are provided as reference examples for the preparation of the compounds of formula (I) mentioned above but not claimed in this application;

Examples of the Beta-Testing of Compounds,

1st oelaaa

2 - ((Methyl) -3- (trifluoromethyl) anisole (208 mmol) 3 - (trifluoromethyl) anisole was dissolved in 500 mL of anhydrous tetrahydrofuran and 100 mL (250 mmol) was added at -70 ° C under nitrogen. ) A 2.5 M solution of bubi lithium in hexane was added slowly with stirring and cooling. The reddish solution was stirred for 1 hour at -70 ° C and then slowly with stirring and cooling in 42 ml (270 mmol) of d If time is added, the reaction mixture is allowed to warm to reflux for 18 hours, shaken with 250 ml of saturated aqueous ammonium chloride solution, the organic phase is separated, dried over magnesium sulfate and concentrated under reduced pressure to give a yellow oil. Fractionation was carried out on a Vegreux column at 27 Pa to isolate the hot fraction at 02 ° C to give 37 g (71 33) of a pure liquid, 32% of the title compound and 10% of the isomeric 2- (propylthio) -5- (trif). Elemental analysis for the C 1 -C 5 S 5 -SFsOS formula:

Calculated: C, 52.8; H, 5.24; S, 12.8.

Found: 52.7; 5.11; 11.0.

1 H-NMR: (CDCl 3): 7.02 (m, 3H), 3.96 (s, 3H), 2.83 (f, 2H, = 7.4), 1.54-1.04 (m, 2H), 0.93 (t, 3H, 3 = 7.4).

Example 2

2- (~ 8enzU tí0) -ansz0Í

2-methoxy-thiophenol (25.0 g, 170 mmol) in 50 mL anhydrous fetrahidrofuránnal added dropwise at ° ^C C, potassium t-butoxide (22.0 g, 198 mmol) in IOO ml of tetrahydrofuran was added with stirring. A solution of benzyl chloride (25 mL, 214 mmol) in tetrahydrofuran (50 mL) was added to the reaction mixture with stirring and then allowed to warm to room temperature and stirred at this temperature for 18 hours. The reaction mixture was concentrated under reduced pressure and the residue was diluted with dichloromethane (300 mL). The resulting solution was washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The title compound is a white solid. Op .: SALT C.

Elementary table for C ^ H-NEW:

Calculated: C, 73.0; H, 8.13; S, 13.9

Found: 73.0; 6.13; 13.7.

¹ H NMR (CDCIg) 7.2 (m, 7H) _S 8.8 (m, 2H), 4.1 (s, 2H), 3.00 (s, 3H).

we

MetiHO-Cpropn-thio-S-methoxy-l

85.3 g (31S mmol) of 3- (4,4-dimethyloxazohn-2-yl) -anisole were dissolved in rabidrofuran, cooled to -70 ° C, and then stirred with stirring for 185.5 mL (414 mmol). 2.5 M Butyllithium was added. The red wine solution was heated to -40 ° C for 90 minutes, then cooled again to -70 ° C and, under stirring and cooling, 82.2 g (414 mmol) of diprophysulfide A solution of 108 ml of tetrahydrofuran was added dropwise, the reaction mixture was warmed to room temperature over 80 minutes, and the suspension was neutralized with 300 ml of saturated aqueous ammonium chloride solution. The residual golden yellow oil was 2x10 cm Yield at 155-157 ° C

Fraction (80 Pa) on a Vigreux column (80 Pa) Hot fraction 78 g (88%) of 2- (propyltlo) -3- (4,4-dimethoxy-oxazolin-2-yl) -anisole, a light yellow oil.

(CDCl3): 7.25 (t, 1H, > 7.8), 7.06 (dd, 1H, 3 = 78,

1.3), 8.80 (overnight, 1H _S3 = 8.3, 1.2), 4.08 (s, 2H), 3.37 (s, 3H), 2.78 (1.2H, 7.2), 1.44 (m, 2H), 1.37 (s, OH), 0.89 (t, 3H, 3 = 7.4),

58.2 g (200 mmol) of 2 ^: - (propyl) -8- (43 ', 4'-ethyl-8-ox: azin-2-yl) -anisole are suspended in 8N aqueous hydrochloric acid and the suspension is kept for 18 hours. while stirring under reflux. The resulting homogeneous solution was extracted with diethyl ether (3 x 100 mL), the extracts were combined, dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting oil was purified by flash chromatography on a silica gel column, eluting with a mixture of beethane-ethyl acetate, The product-containing fractions were combined and evaporated under reduced pressure to give 38.7 g (82%) of 2- (pr -). methoxybenzoic acid, a viscous golden yellow oil.

(COCl 3): 12.3 (broad s, 1H). 7.55 (dd, 1H, > 7.8, 1.1), 7.33 (t, 1H, > 8.1), 7.01 (d, 1H, > 8.3, 0.9) , 3J 2.80 (t, 2H, > 7.5), 1.49 (m, 2H), 0.80 (t, 3H3 = 7.3).

1?

38.1 g (169 mmol) of S-propyl-fluo-δ-methoxybenzoic acid are suspended in 100 g (843 mmol) of thionyl chloride and the suspension is stirred for 18 hours. The solution is concentrated under reduced pressure to give 39.7 g of crude acid chloride. . A 8.7 g portion (38 mmol) was dissolved in 100 ml of anhydrous methanol, and the solution was cooled to 0 ° C with 4.7 g of <

and mixing and cooling. At the beginning of the reaction, the reaction was quenched under reduced pressure for one hour and dissolved. The ether ol

moles) of TetU-amine ether to warm, and the reaction mixture was then washed with two 200 ml portions of water and washed with water to reduce the yield; 8.4 g (99%) of the title compound, a dark oil, 1 H-NiFr (CDCl 3): 7.26 (t, 1H, 3 = 8.2), 7.03 (d, 1H, 3 = 8). , 9), 8.9 (d, 1H, 353 = 8.2), 3.87 (s, 3H), 2.77 (1.2H, 3 = 7.4), 1.45 (m, 2H), 0.89 (t, 3H, 3 = 7.4).

-S-Cprcpd-t io) -4 ~ (trifl uor-metU) ~ pyrid in

A solution was prepared using 1 L of methyl ethyl and 7 L of anhydrous THF and cooled in a dry ice / acetone bath. To this solution, while cooling and stirring, 12.4 g (70 mmol) of 2-

^? mmool) Duzopropniuk to warm to -40 ° C, then dry and add 33 ml of methoxy-4- (trifluoromethyl) pyridine and 0.92 m-amine with stirring and cooling. Dipropyldisulfide (210 mmol) was added dropwise with an ice / acetone bath. After allowing the mixture to warm to room temperature, extract with water (189 ml) and diethyl ether. The ether extract was dried over magnesium sulfate and concentrated under reduced pressure. The brown oily residue was purified by chromatography (adsorbent silica gel; eluent: hexane-ethyl acetate mixture).

Yield: 14.1 g (80%) of the title compound, a light yellow oil.

Elemental Analysis for C10H12NF3O5S;

Calculated: C, 47.8; H, 4.81; H, 5.57: 8, 12.8;

Found: 48.1; 5.33; 5.33; 12.7.

(CDCl 3): 8.18 (d, 1H, 3 = 5.7), 7.12 (d, 1H, d = S, 7),

4.00 (s, 3H), 2.85 (t, 2H, 3 = 7.4) .. 1.97-1.46 (m, 2H), 0.93 (1, 3H, 5 = 7, 2)

Similarly prepared was the following 3- (propo-thio) -pyridine-n2-methoxy-S-C-propyl-thiol-pyridine, colorless 80 ^on C-hot boiling point;

Elemental Analysis for CgHnOS Calculated G% 59.0; H, 7.15.

Found: 59.1: 7.12;

- k I · r ·· 4 - met ο χ I ~ 3 ~ (p ro ρ ί I ~ tí 0) - ρρ ri dl n, one fist (CÖCI3): 8.21 (d, 1H, d = S, 6), 6.77 (d, 1H, 3 = 5.8), 3.97 (s, 3H), 2.85 (t, 2H, 3 = 7.5), 1.57-1 , 50 (m, 2H). 0.99 (t, 3 = 7.3); and? -chloro-4-methoxy-S-CpropH-10-yl-pyridine-yellow oil 1 H-NMR (CDCl 3); 7.96 (d, 1H, 3 = 5.2), 8.98 (d, 1H, 3 = 5)

4.02 (s, 3H), 2.88 (t, 2H, 3 = 7.3), 1.54-1.51 (m, 2H), 0.96 (1.3H,

3 = 7.8).

metih-fluoro-benzenesulfonyl-chloro

A mixture of 20.0 g (80 mmol) of S-propylthio-S-Cinfluoromethyl-O-snizok-O-propylthio-e-trifluoromethyl-anisokismereflen component 80.10.8 is mixed with 250 mL of chloroform and 125 mL of water the mixture was cooled to 0 ° C with an ice bath and slowly while stirring

Chlorine gas (21.6 g, 305 mmol) was introduced into the mixture. After 2.5 hours, the organic phase was separated, dried over magnesium sulfate and concentrated under reduced pressure. The residual clear oil was mixed with 100 ml of pentane and allowed szobahömérsékleíen stand for 18 hours, followed by crystallization in a refrigerator for 3 hours, filtration of the precipitated solid material was the title compound (11.0 g, 54%) as white crystals ¹ H NMR ( CDCl3); 7.8 (dd ₎ 1H, 3 = 7.8, 8.6), 7.53: 86-88 ° C. 1H, δ = 7.8),

I, 1H, 3 = 8, is.

Ida

- M e 1 oxl -be η ζ ο I - s z u I f ο η 1 I - k 10 r I d

34.1 g (140 mmol) of 2- (benzoyl) -anisole are dissolved in 300 ml of chloroform, 150 ml of water are added and the mixture is cooled in an ice bath. 39 g (550 mmol) of chlorine gas are added while cooling and stirring. allowing the temperature below 5 ^C to leave the yellow and yellow reactor to warm to room temperature and then 18 hours

The phases are separated, the chloroform phase is dried over magnesium sulfate and concentrated under reduced pressure. The residual oil crystallizes on standing.

Yield: 21.3 g (69%) of a white crystalline compound. M.p. 52-53 ° C.

(CDCl3): 7.93-7.76 (m, 1H), 70-7.65 (m, 1H), 7.13 7.08 (m, 1H), 4.0 (s, 3H).

7. pId a

Μ © ίΐΙ "[2 ~ (ΚίόΓ-δ2υ1ίοηΐΙ) 3 ·· σΐ6ίοχί 0 © ηζοά1]

A mixture of 7.8 g (32 mmol) of methH- [3-methoxy-2- (propyl) benzoate, 2.3 g (130 mmol) of water and 30 ml of glacial acetic acid was heated to 45 X

7.5 g (107 mmoles) of chlorine gas were introduced into the mixture with stirring. The dark mixture changes color to light orange and the temperature rises to 75 'X. After 1 hour, the reaction mixture was poured into 800 ml of ice water and the mixture was stirred until the ice was melted. The solid was collected by filtration, dissolved in 500 ml of diethyl ether, dried over magnesium sulfate and concentrated under reduced pressure. The yellowish-brown residue was purified by flash chromatography (adsorbent: silica gel; eluent; hexane / ethyl acetate). The eluate fractions containing the product were combined and concentrated under reduced pressure.

Yield: 5.342 g (62%) of the title compound as a light pink crystalline solid. 106.5-108.5 X.

Elemental Analysis for 0§Η _δ 0ΙΟ $ 6:

Calculated: C, 40.8; H, 3.43; 8%, 12.0;

it: 40.7; 3.62; 11.8.

1 H-NyR (ODCl 3): 7.88 (t, 1H,> 8.0),? 41 (d, 1H,> 8.7), 7.03 (d, 1H, 3 = 7.5), 4.05 (s, 3H) _: 3.90 (s, 3H)

2.8 - Dl m e 10 x í - b e η ζ ο I - s z u í f ο η 11 - k le r i d

15.0 g (108 mmoles) of 1,3-dimethoxybenzene and 13.8 g (119 mmoles) of NMNkN'-tetramephylethylenediamine are dissolved in 225 ml of dry petroleum ether. The solution was cooled to 0X and 47.5 mL (119 mmol) of 2.5 mL of butyllithium in hexane was added with stirring. After 1 hour, the mixture was stirred for ca. Cool to -72 ° C and add, while stirring, about 70 g (1 mol) of sulfur dioxide in the form of a saturated solution in 100 ml of dichloromethane. The resultant light yellow flour was heated to 10 ° C over 2 hours to give a sticky The yellow solid was filtered, washed several times with anhydrous diethyl ether. The solid was slurried in 400 mL of anhydrous hexane, the slurry was cooled to 0 ° C and 14.6 g (108 mmol) of nascent l-clone in 200 mL of dry hexane was added. After 45 minutes, the resulting pink solid was filtered at 0 ° C, washed with cold hexane and dissolved in ether. The solution was washed with three thousand 150 mL cold water, dried over magnesium sulfate, filtered and concentrated under reduced pressure.

Yield: 19.4 g (76%) of light yellow crystalline title compound. M.p. 89-91 ° C.

(COGI3): 7.51 (1H, O = 8.5), 6.84 (d, 2H, O = 8.5),

3.82 (s, 6H).

In a similar manner, the following compound was prepared:

2,4 ~ d i m e t ο χ -p -pyrid In-3 z u í f ο η ί I - k 10 r I d, which is a yellow solid is a solid. Mp 118-120 ° C.

1 H-1MMR (CDCl 3). 8.26 (d, 1H, O = 5.8), 6.68 (d, 1H, O = 5.0),

4.11 (s, 3H). 4.05 (s, 3H).

I-5-m et 11-be nzo I -s z u If on H-cl 0

4-Ethoxytoluene (6.8 g, 50 mmol) was dissolved in dichloromethane (20 mL). The solution was added at 0 ° C with stirring and cooling to a solution of chlorosulfonic acid (10 ml, 150 mmol) in dichloromethane (10 ml). The reaction mixture was stirred for 1 hour at 0 ° C, then warmed to room temperature and stirred for another hour. The tan solution was poured into ice water (206 ml) and the reaction mixture was stirred

extract the title compound with dichloromethane. The extract was dried over magnesium sulfate and concentrated under reduced pressure to give 7.9 g (68%) of a light ski compound. M.p. 58-61 ° C 1 H-NMR (CDCl 3): 7.71 (d, 1H, 3 = 2.2), 7.4 (dd, 1H,> 8.5, 2.2), 1d), 1.49 (t, 3H, 3 = 7.0).

0's

100m

A solution of 2-methoxy-4- (trifluoromethyl) pyridine-3-sulfonic chloride in 60 ml of 2-methoxy-3- (propylthio) -4- (trifluoromethyl) mol. with water, cool the mixture in an ice bath. Chlorine gas (5.1 mL, 112 mmol) was slowly added to the mixture under cooling and then allowed to warm to room temperature and the mixture was stirred for 3 h, the organic phase was stirred with magnesium sulfate and the like. The effluent was evaporated under reduced pressure. Purify by chromatography (adsorbent; silica / ethyl acetate). The product is concentrated and concentrated under reduced pressure.

I; eluent: hexane mm elution:

%} title let, which is clear

H NívIR

3) 18 8.6 (d, 1H, O = 5.4), 7.4 (d, 1H,> 5.4), 4.2 (s,

Ms: molecular ion peak M 275,

Similarly, the following plridm-3-sulfonyl clonde derivatives were prepared;

α-chloro-N-methoxypyridine-5-sulfone- ¹ H-NMR (CDCl 3): 8.23 (d, 1H, δ = 5.6), 7.11 (d, 1H, ≥ 5.2) ). 4.17 (s, 3H);

Also: Molecule Ion peak kT 275, g-Chloro-4-methoxypyridine-S-sulfone-H-clay salt crystal (CDCl 3): 8.47-19, M

1H,

4.13 (s, 3H) and

S-methoxypyrimidine-S-sulfonyl chloride as a clear oil 1 H-1 H NMR (COCl 3): 8.48-8.49 (dd, 1H, JM, 9, 4.9), 3.22-8.19 (dd, 1H, 3 = 1.9, 7.8), 7.08-7.04 (dd, 1H, 3 = 4.9, 7.8), 4.18 (s _s 3H) m.p. (1,1,2,2 ~ (Tet for u 0 r - et ο xi)] in zol - su lf ο η I1 - k le rid

Sodium nitrite (3.8 g, 55 mmol) in a solution of 8 mL of water was added with stirring and cooling to 12.3 g (50 mmol) of 2 »

- (. 1,1,2,2 ~ (~ tetrafluoro etcxi) j anllin, 18 ml of concentrated acetic acid and 8 ml sósavaidat -10 ^c C ~ precooled was added th the obtained mixture, 1.3 g mmol) in minutes To a solution of cupric chloride and 0.5 g (4 mmol) of cupric chloride in 50 ml of sulfur dioxide (more than 12 g) saturated acetic acid was added at -10 ° C. The reaction mixture was warmed to room temperature, stirred for 90 minutes and then poured onto ice. The resulting mixture was extracted with diethyl ether and the extract was dried over magnesium sulfate and concentrated under reduced pressure. The residue was chromatographed on silica gel and eluted with hexane-ethyl acetate. The product-containing fractions were combined and concentrated under reduced pressure.

Yield: 11.0 g (75%) of the title compound as a yellow oil.

, Ί Η, 3-1.7,

7.78

3-1.7, 7.8, 8.1), 7.50 (dd, 1Η _; 3-1.2, 8.1), 7.45 7.8, 8.0), 8.05 (judgment, 1Η, 3-4.0, 58.0).

Ms: ionic molecule M ⁺ 292.

IR, 3-1.2,

3-Amino-8-Rlór-5- (methylthio, phenylthio) _(1.2! 4jtriazolo [4,3-c] pirimidinml (120 mmol) of 3M methylene mefános cyan mmol) of 5-chloro <4 hídraxino-2 A solution of (methylthiopyrimidine) in 200 ml of anhydrous isopropanol was stirred at room temperature with stirring. The reaction mixture was stirred for 18 hours and then diluted with 500 ml of diethyl ether. The precipitated solid was collected by filtration and dried. m.p.> 250 ° C.

Elemental analysis for CgH / NsBrCIS:

Calculated: C, 24.3; H, 2.38; M, 23.8; S, 10.8 Found 28.1, 2.69; 24.0; 12.2 tR-RMR (OMSO-d6): 7.80 (s, 1H); 2.87 (s, 3H);

13C-NMR; 150.98, 147.90, 143.10, 138.38, 113.18, 14.22.

Similarly, the following 3-amino (1,2,4) trlazolo [4,3-c] pmmide in derivatives were prepared:

3-amino-8-fluoro-5- (methylthio) - [1,2,4] triazolo [4 _3-c-s pi rhyme pyrrolidine hydrogen brormd which a yellow solid. M.p. 188-170 ° C. Elementalization for CsH? HsBfFS:

Calculated: 0% 25.7 H% 2.51 N% 25.0 S% 11.4 Found: 25.7 2.52 25.0 11.5

3-Ammo-8-methoxy-5- (methylmethyl) - [1,2,4] triazolo [4,3-c] pyrimidine m-bromide, which is a tan solid, m.p.

Elemental analysis for C ₇ Hs ₀ N _s BrO8:

Calculated: C, 28.8; H, 3.45; N, 24.0; S, 11.0; 3.44; 23.9; 11.1:, 3-O-pyrimidine-3-amine-8-d - 5-hydrobromic acid, which is a yellow solid. Op .: 197 Analyzes for CgHzNgBrlS:

, 1 ',: 193-195 ^Ö C.

Calculated: C% 18.3 Found 19.0

- m-o-8-value m -5 - (methylthio) hydrobromide, which is a yellow solid Elemental analysis for CeHyNgBrgS:

Calculated: C, 21.1; H, 2.07; N, 20.8; 8%, 9.40. Found: 21.3, 2.14, 20.6, 9.33.

3-Amo-8-methN-5- (methylthio) - (1,2,4] pyriazolo [4,3-b] pyrimidine bromide which is a yellow solid, m.p. 234-238 ° C.

Eumanalysis of E ·? Η «4

Calculated: 0% 30.8 H 3.30 N% 25.5 S 11.7 Found: 30.7 3.82 28.3 11 ₅ S

3-Amino-5-eth.xi-5-methyl-thio} -1,2,4] triazolo [4,3-b] biobromide which is a yellow powder. 160-183 ° C.

3-Amino-5- (methylthio) -b1,2,4] triazolo [4,3-b] bromide, which is a brownish yellow solid.

1 H-NMR (DMSO-d 6): 7.52 (d, 1H, 3 ^ 3.8), 7.13 (<

6.08 (s, 2H): 2.81 (s, t, 3-8.7),

- Am I η-8- Ki-r-5-methoxyl- [1,2,4] t1 azolof 1,5-c] pl nmld In

15.0 g (51 mmol) of 3-amino-8-chloro-5- (methylthio) [1,2,4] thiazolo [4,3'-e] -minimidinium-hydrobromide, 8.2 mL (78 A mixture of ethyl acrylate (100 mmol) and methanol (100 mL) was cooled in an ice bath, and a solution of 4.5 M sodium methoxide (17 mL, 76 mmol) in methanol was added slowly, with stirring and cooling, and allowed to warm to room temperature for 18 h. After stirring, the reaction mixture was neutralized with acetic acid (2 ml) and the solid was collected by filtration, washed with diethyl ether and dried.

Yield: 7.7 g (75%) of the title compound as a tan powder. Mp: above 250 ° C.

Rleman analysis for CeHgNgCIO:

H, 3.03; N, 35.1 Found: 36.1 3.19 34.8 (DMSO-d 6); 8.0 (s, 1H), 6.8 (s broad, 2H), 4.1 (s oe, 188.40, 151.85, 147.73, 140.95, 108.57, 58.12). We have prepared the following 2-amino (1,2,4} 1Π3ζοΙο [1,5- ο] ρ I rim I dl n:

2-Amino-8-fluoro-5-methoxy [1,2,4] triazolo [1,5-c] pyrimidine, which is a tan crystalline solid with a melting point above 230 ° C. Elemental Analysis for C $ H _s NsFÖ:

Calculated: C% 39.4 HM 3.30 NM 33.2

Found; 39.5 3.28 37.7

2 ~ ηηΉ0ο-5,8 ~ 8ΐΓηοίοχΙ ~ [1 _: 2,4] triazolo [1,5 ~ ojplrlmIdIη, which is a tan powder. m.p .; 201-203 ° C.

An example of CrHgNgOa is:

date; C, 43.1; H, 4.85; N, 35.9

Found; 43.2 4.87 35.5

2-amino-7-fluoro-5-methoxy [1,2 _t 4] triazolo [1 _t 5 -c] pyrimidine

Eiemanallis for ΓΟ $ Ο _δ Η * .ΓΟ;

H, 3.30; N, 38.2

Found; 39 _s 8 3.31 38.2

2 »amínO'8-iodo-5-methoxy [1,2,4Jtríazoio (1,5-cjpínmidín that this tan solid with a melting point above 250 ^U C · Eiemanallzis the CgHsNglö calcd;

date; C, 24.8; H, 2.08; N, 24.1 Found; 25.0 1.96 23.8

- am ino -8 - me 11I - 5 »met ο χ I [1,2,4] tr I azile 11.5 ~ c} ρ I r 1 m I d I a brain tan solid above 250 ° C melting points. Eiemanallzy for CyHgNgÖ:

Calculated: C, 46.9; H, 5.08; N, 39.1

Found: 46.7 4.84 39.1

- am I no- 8 - et o - 5 - m et o (1,2,411 r 1 azo 1,5 - c | p I r I m in, me or a light tan solid. Op. 190-191 ^Ö C and

2-Amino-5-meloxy [1,2 ₍ 4] triazolo [1,5-a] pyrimidine, a tan solid with a melting point above 250 DEG C. (D SOSO ds): 7.82 (d, 1H, 0 = 6.3), 7.03 (d, 1H, 3 = 8.1), 8.31 (S, 2H) and 4.12 (s, 3H).

2- [Ν ~ {1ΠΓΠ © 1ί! -ΔΖίΙΠ ~ 3ΓηΙηο)] - 8-Μ0Γ-5-Γηβ1οχί ~ [1,2,4} thiazole [1,5-c] pirlm idin liter in a dry flask under nitrogen 12.7 Sodium iodide (85 g) (85 mmol) and anhydrous acetonitrile (425 mL) were added and stirred under stirring at room temperature with 9.25 g (10.8 mL, 85 mmol) of t-dorodomethylsilane, and after 10 minutes, 17.0 g of 85 mmol) of 2-amino-8-chloro-5-m: ethoxy- [1S, 5'-trimethylsulfonyl-5-methyl] -amine and 8.82 g (11.9 mL, 85 mmol) of written amine are added with stirring, The reaction mixture was stirred for 12 hours at room temperature and then diluted with 500 ml of anhydrous diethyl ether. The precipitated much dried sintered filtrate under reduced pressure;

lithium ether, diluted with urine filtration. The residue is taken up in an additional 530 ml of anhydrous and the salt is repeated as an aliquot. Yield: 19.5 g (Example 84)

The compound N- (8-Chloro-5-methoxy- [1,2,4] triazolo [1,5-c] pyrimidin-2-yl) -2-methoxy-8- (fluoromethyl) -benzenesulfonamide

Dissolve 19.5 g (72 mmol) of 2- (N- (trimethylsilylamino)) - 8-chloro-5-methoxy- (1- ₍ 23Mnazolo [1,5-ol) in 150 ml of anhydrous acetone) and add under stirring, under nitrogen, at room temperature, 27.5 g (100 mmol) of 2-meloxy-8- (fluoromethyl) -benzenesulfonyl chloride were added to the reaction mixture with stirring, 8.7 g (8.9 ml, anhydrous pyridine, followed by addition of 0.88 g (0.80 mL, 8.5 mmol) of anhydrous dimethylsulfoxide and 13.7 g (85 mmol) of cesium fluoride were added and the reaction mixture was stirred for 8 hours. The solid was first filtered into methanol and filtered. The white solid was dried to give 21.3 g (88%) of the title compound.

Calculated for C C hHH mNmClFjO ^S: C, 38.4; H, 2.53; N, 18.0.

18.1

- (8-Chloro-5-methoxy [1,2,4] tnazoio [1,5 ~ cjpírimídin-2-yl) ~ 2, e ~

0.80 g (4.0 mmol) of 2-amino-8-chloro-5-methoxy [1,2,4] triazoSo [1,5] pyrimidine was suspended in 15 ml of anhydrous acetonitrile and stirred at room temperature for 1.80 g (8 ml). , 0 mmol) 2, δ-ά! Γη «1οχί-06ηζοΙ-5ζηίίοηίΜ <ΙθΓ5Ρο1, 0.83 g (8.0 mmol) of anhydrous pyridine and 0.08 g (1 mmol) of anhydrous dimethyl sulfoxide are added while the system is keep it dry. After 18 hours, another 0.32 g of anhydrous pyridine was added. and after another 18 hours

0.01 anhydrous dimethylsulfoxide is added to the reaction mixture. After an additional 1 h, the reaction mixture was diluted with dichloromethane (350 mL), washed with water (3 x 150 mL), dried over magnesium sulfate, filtered and the filtrate evaporated under reduced pressure, m.p. 215.5 · uk. The remaining orange oil gave a light yellow solid m <

mining; 1.41 g (88%) of the title compound

217.5 ° C.

Elemental Analysis for C ^ HuHNNNsCIOsS Calculated; C, 42.1; H, 3.53; N, 17.5; S, 802 Found: 42.2 3.02; 17.1 7.70 (δMSO-d6); 11.74 (S, 1H) 8.10 (s, 1H), 7.44 (t, 1H, = 8.5), 8.75 d = 8.4), 4.11 (s, 3H), 3.88 (s, 3H), 3.77 (s, OH),

O-Carbomethoxy-e-methoxy-N-C 5 H -dimethoxy-n, 2,4-triazolone, 5 p 3 ρ I r i m i n - 2 ~ 11) ~ b e η z ο I - s z u ff ο n a m I d

0.70 g (3.5 mmol) of 2-amino-5,8-dimethoxy [1,2 _s 4] triazolo [1,5] cpm was suspended in 15 ml of anhydrous acetonitrile, and 1.8 g (7 g) were added to the suspension with stirring at room temperature. (0 mmol) meflM2- {chloro-5-sulfonylGnH} -3-methoxybenzoate], 0.55 g (7.0 mmol) of anhydrous pyridine and 0.07 g (0.9 mmol) of anhydrous dimethyl sulfoxide are added. After keeping the system dry, after 18 hours, another 0.92 g of anhydrous pyridine and 0.07 g of anhydrous dimethylsulfoxide were added to the reaction mixture, and after another 38 hours, an additional 0.92 g of anhydrous pyridine and 0.92 g of anhydrous pyridine were added. g of anhydrous pyridine and 0.07 g of anhydrous dimethyl sulfoxide are added. After an additional 18 hours, the reaction mixture was diluted with dichloromethane (300 mL). trituration with ether to give the title compound as a white solid of 80% purity. This was chromatographed twice on a silica gel column eluting with dichloromethane / ethanol / acetic acid as the mobile phase, with little success. then recrystallized from hot methanol.

Yield: 0.274 g (19%) of a bright white crystalline product. Op 215-217 ^e C.

Elemental analysis for CisHitNsOtS:

im% 45.4 H% 4.05 N%

8%

Found:

44.7 L, d ^; ;, 3), 7J

3.96 18.2 7.83 i: 11.78 (s, 1H), 7.80 (t, 1H, 3 = 8.3), 7 28

1, 3 = 7.8), 4.07 (s, 3H), 3.88 (s, 3H), 3.8 (s, 3H) <3.78 (s, 3H).

0 (1,5unk and a

2.8 ~ Dimethoxy "N- (5,8-dimetcxí ~ l 1 2 _J! 4lfriazolo (1,5-cjpirimidin-2-yl) benzene-sulfo ~ genital

0.80 g (4.1 mmol) of 2-amino-5,8-dimethoxy- (1,2,4] trh) -pyrimidine in 15 ml of anhydrous acetonitrile;

with stirring at room temperature) 2,6-dimethoxybenzenesulfone H-chloride, 0.55 g (8.2 mmol) anhydrous pyridine and 0.08 g (1 mmol) anhydrous dimethyl sulfoxide are added while the system is kept dry . After 24 hours, the reaction mixture was diluted with dichloromethane (200 mL). The organic layer was separated, washed with water (2 x 200 mL), 2N aqueous hydrochloric acid (2 x 200 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo.

Element Analysis for CtsHnHsÖeS:

Calculated: C, 45.8; H, 4.33; N, 17.7. Found: 45.7; 4.19; 17.8 ¹ H NMR (DMSO-d 6): 11.54 (s, 11 d = 8.4). ), 8.74 (d, 2Η, 3 = 8.4), 4.08 (s, 2

Example 19

2-Methoxy-5-methyl-N- (5,8-dimethoxy- (1,2,4] triazolo (1,5-c} pyrimidin-2-yl) -beta n-l-sulfone If ο n a m id

1.0 g (5.1 mmol) of 2-amino-5,8-dimethoxy-1,2,4-triazolo [1,5-c] pyrimidine and 2.1 g (10 mmol) of 2-methoxy-5-methyl-benzenesulfonyl; · -Cladd was mixed with 15 ml of anhydrous asphonite and 0.8 ml (10 mmol) of anhydrous was added to the mixture while stirring at room temperature.

7.55 (s, 1H), 7.44 (t, 1H), 3.78 (s, pyridine, and 71 cl (1.0 mmol) in anhydrous dimethylsulfoxide) while keeping the system dry for 18 hours. After stirring, another 1.0 g (5.0 mmol) of S-methoxy-S-methyl-benzene · sulfonate chloride was added, stirring was continued for another 24 hours, and again 0.4 ml of anhydrous pyridine and Stirring was continued for a further 9 days, then the volatiles were evaporated under reduced pressure, the dark residue was diluted with water (50 mL) and dichloromethane (50 mL) and the solid was collected by filtration. -methane and after stirring for 2 hours, filter.

Yield: 1.2 g (63%) of the title compound as a white powder, m.p. 217-219 ^C O.

Elemental Analysis for CisHrzNsQgS:

Calculated: C, 47.5; H, 4.52; 18.5; S, 8.45

Yields: 47.7 4.61 18.3 8.80

UNMR (OMSO-d 6): 12.9 (bs, 1H), 8.1 (s, 1H), 7.7 (t,

IH. 4 = 3.2), 7.58-7.52 (m. 2H). 4.08 (s, 3H), 4.1 (s. 3H), 3.9 (s,

3H);

Example 20

N- (5,8 ~ dimethoxy ~ [1.2,4jtriazoío [1,5'-cjpirimídín-2-yl) ~ 2-methoxy-4- (trifluoromethyl ~ ylmethyl) ~ pyridin ~ 3-sulfonamide

0.75 g (93.8 mmol) of 2-amino-5,8-dimethoxy- [1,2 ₍ 4) benzyl] [1,5] -pyrimidine and 2.1 g (7.6 mmol) of 2-methoxy-4- (Trifluoromethyl) pyridine-3-sulfonyl chloride was added with 10 mL of anhydrous acetonitrile and 0.61 mL (7.8 mmol) of anhydrous pyridine, 43 of (0.6 mmol) of anhydrous dimethyl sulfoxide and a small amount of dry 4A molecule sieve was added while ensuring moisture was removed and the reaction mixture was stirred for 5 days, followed by another 1.0 g (3.4 mmol) of 2-methoxy-4- (trifluoromethyl) pindm-3-sulfonyl chloride. and 0.30 ml (3.5 mmol) of anhydrous pyridine were added and stirring was continued for 2 days, at which time 8.30 anhydrous pinam: adun * was added to the reaction mixture, which was further diluted with Dormethane and stirred for two days. The pre-mixture is washed 10 times with 100 ml of 2N aqueous hydrochloric acid solution, dried over magnesium sulfate and concentrated under reduced pressure.

Today, the solid residue is chromatographed on staggel; eluent: dichloromethane / ethanol).

mining; 0.90 g (84%) of the title compound is a solid. M.p .: 214-218 C. ^e

Elemental Analysis for: CuHmNgFsOsS: Calculated; C% 38.7 H% 3.02 19.4 S <7.3f

Found: 38.5 3.15 19.4

7th

r su

g): 12.3 (broad s, (d, 1H, 3 = 5.3),

7J (m, 2H), 4.08 (s, 3H), 3.95 (s, 3H), 3.85 (s, 3H),

2- (Methoxycarbonyl) -8-methoxy-H- (5-chloro-8-methoxyl, 2,4] tri-azo [1,5-a] -plid in-2 -11} - η ζ ο I - szu Ilona m I d

0.90 g (4.5 mmol) of 2-amino-5-chloro-8-mexyl- [1,2,4} triazolo [1.5] v and the aripyridine in 35 ml of anhydrous acetonitrile under stirring at room temperature 2, 38 g (8.05 mmol) of methyl H 2 · 3 - (chlorosulfonyl) -3-methoxybenzoate. Anhydrous pyridine (5.72 g, 9.1 mmol) and dimethylsulfoxide (0.071 g, 0.91 mmol) were added while the system was kept dry. After 15 hours, another 0.35 g (4.5 mmol) of anhydrous pyridine was added and after 1 hour the volatile components were evaporated under reduced pressure. The residue was diluted with dichloromethane (50 mL) and 2N aqueous hydrochloric acid (50 mL) and stirred vigorously for 72 hours. The solid was collected by filtration, water (3 x 25 mL), dichloromethane (3 x 10 mL), and 10 mL (3 x 10 mL).

The filtrate and washings were combined and diluted in a separatory funnel with 25 mL of dichloromethane and 25 mL of 2N aqueous hydrochloric acid. The phases were separated and the organic phase was washed with 3 x 50 mL of 2N aqueous washed with brine, dried over magnesium sulfate, filtered and the filtrate evaporated under reduced pressure to give a yellow solid. This was suspended in dichloromethane (5 mL), the solid was collected by filtration, washed rapidly with dichloromethane (2 x 5 mL) and dichloromethane (2 x 15 mL) to give the title compound as a white solid. The combined product was 1.09 g (56%), m.p. 290-292 ° C (dec.).

Elementalization for CuHisN ^ C10SS:

date; % C 45.0% H 3.45% N 7.51% S Taíáít 13.1: 44.9 3.39 12.8 7.79 ^1H-NMR (DMSO-dg) 11.60 <s, IH) , 7.82 (t, 1H, 3-7.69), 7.24 (m, 2H), 7.05 (m, 2H), 3.92 (s, 3H), 3.83 (s, 3H). ), 3.77 (s, 3H),

2- (Methoxy-carboxylic II) -5-methoxy-N- _(5, 6-d im ethoxy (1,2,4] triazolo [1 5-ajplrldln-2 "H) _{-benzenesulfonamide}

In a dry flask fitted with a glass and rubber stopper, 0.871 g (2.04 mmol) of 2-methoxycarbonyl-6-methoxyl-N- (5-chloro-8-methoxyl- (1,2,4) diazolo [1,5- (a) Pinnin-2-U) -Benzenesulfonamide was added to the contents of the sealed flask with cannula (20 ml) in dry dimethylsulfoxide (1.00 ml) and 6.12 M sodium methoxide in methanol (1.39 ml). After 18 hours, another 0.050 ml of sodium methoxide was added to the reaction mixture and the reaction was allowed to proceed for another 16 hours. The reaction mixture was then acidified with glacial acetic acid and quenched with 200 ml of dichloromethane. The filtrate was evaporated under reduced pressure to give a white solid, which was dissolved in 600 ml of dichloromethane and purified by column chromatography (adsorbent; The product-containing fractions were combined and concentrated under reduced pressure.

mining; 496 mg (57%) of an ohm which is an off-white solid, m.p. 274-2: 76 ° C (dec.).

To email this to CvH-.ghbOyS:

date; C, 48.3; H, 4.30; 13.3; S, 7.59

Found: 48.6 4 26 13.1 7.83 (OMSO-d6): 11.33 (s, 1H), 7.61 (t, 1H, 3 = 6.05), 7.28 (d , 1. 4, 8.81), 7.92 (d, 2H, 4 = 7.94), 6.42 (d, 1H, 4 = 8.55), 3.98 (s, 3H). 3.85 (s, 3H), 3.82 (s, 3H), 3.75 (s, 3H).

Evaluation of the Post-Emergency Herbicidal Activity The seeds of the desired test plant were planted in Grace-Sierra MetroMix® master mix (typically pH 6.0-6.8; organic content about 30%) using 84-surface plastic pots. Where necessary, fungicldes and / or other chemical or physical treatments have been used to promote germination and plant health. The seedlings were kept in a greenhouse for 7-21 days, where the plants were exposed to light for about 15 hours a day, and the temperature was 23-29 ° C during the day and 22-28 ° C at night. Plants received nutrients and water on a regular basis, with additional illumination (overhead watts of halogen bulbs above) as needed. The plants were considered ripe for testing when the first or second true leaf appeared,

Depending on the maximum amount to be tested, a given amount of each test compound was weighed into a 20 mL glass vial and dissolved in 4 mL of 97: 3 v / v aoetone and dimethylsulfoxide to produce concentrated stacks. Optionally, the dissolution was assisted by heating with ultrasonic treatment of live, aoetone, water, isopropanol, dimethyl sulfoxide, 48.5: 39: 10: 1.5: 1.0: 0.02 (v / v). Spray solutions of known concentrations were prepared by diluting with a mixture of atpius 411F vegetable oil concentrate and triton X-055 surfactant,

The highest concentrations of the solutions to be tested are equilibrated with a mixture of 2 ml aliquots of the strain with 13 ml of hot water.

suitably smaller amount of data would be used incení made this way!

5 ml of ahkvot was sprayed uniformly on the spray plants using a DeVilbiss nebulizer operating with compressed air of 140-280 kPa to achieve even coverage. Control plants were sprayed in a similar manner with an aqueous mixture of hsgltö. Corresponds to 1 g / ha.

Treated and control plants were maintained in the greenhouse as described above and watered from below to avoid decay of the test compounds. After 2 weeks, the treated plants and the control were visually compared and scored on a scale of zero to 100%, A nual means that the weed is not damaged and 100% represents complete eradication. Table 2 illustrates the potency of the compounds of formula (I) which were prepared using the compounds of the present invention.

Table 2

Postemergent herbIοId

VsgyW WKS53 S '.'! Sis ? rsa .0 * <v HK BW ZB MQ SWV: GL : BW FIS WV zt SWVi 0 BEE ss GW3 LG GW TT GW OX G '<W O ~ 42 15.6 100 ISO ? s 00 §5 neither 53 7S 75 40 20 75 46 62.5 ICO 75 neither ; tcc. 188 55 SS 70 : _{? δ} 45 55 167 - - - - - i .....-..... - .. r - - - '' '...... 185 2.8 85 toc 55 75 salt 75 80 S8 58 8 8 0 n? ......lake 75 i® ..... §0 80 ? s • V 3 ? 5 0 ANCESTOR 8 0 18S ...... iy..j - ICC 55 75 78 75 $ 83 8 28 e 8 t.58 3U 73 88 85 60 SS 85 75 90 40 38 10 33 289 30 tco 98 V 78 55  80 85 58 • W - 4 ....... 0 228 - r .THE............ - . · - L- 236 - - - - ... - V ............ i - ..the:,,.,,,,... · l - 1237 - - - .. '........ - - - .. - Í -s 1238 The é; i - - - 7 - - - - - Γ- '' ^:

8WCHK - hen string (Stella's media)

8WLMQ ~ White Goose Top (Chencpcalum album)

8WPSG - Hairy Pig ParabitsAmaranlhus retrofSexus) 8WVI0 - Triangular Pansy (Viola tricolor)

GWSLG ~ Scalps (Alopecurus mycsaroidss) GWROX «Sorghum (Sorghum blcöior)

BWCKS - Buckthorn (Xaníhium strumaríum) BWMGL - Ipemoea hederacea

BWVEL = giant moth (Abutihon íheophrasU) BWW8 & A azulakeserbfb (Polygonum convoivulus) GWGF7 = giant muhar (Seíaria faberi)

GWWOT ~ wild oats (Avara village a)

Example 24

Evaluation of the Pre-Toxic Effect The seeds of the desired test plant were adhered (adulterated, soluble component,% clay, 38% sand; pH ca. 8.1; organic matter). content;

1.5%) and sand 70-30; proportion. The soil matrix is placed in plastic pots with a surface of 161 cm. If necessary, fungicides and / or other treatments or physical treatments were used to ensure good germination and plant health.

Depending on the maximum amount to be tested, a certain volume of each test compound is weighed into a 20 ml glass vial and dissolved in 8 ml of a 97: 3 by volume mixture of acetone / dimethylsulfoxide to form a concentrated stock solution by mixing and stirring. . The stock solution was then 99.9; 0.1% water / Tween ^ 155 surfactant solutions of known concentration. The highest concentrations of the solutions to be tested were prepared by adding 5.5 ml of diluent to a 4 ml aliquot portion of the stock solution, diluting the aliquot portion appropriately with the saline solution to prepare solutions with a smaller concentration. Each implanted pot was uniformly sprayed with 2.5 ml of solutions of known concentrations

with a part of the dog, spraying vornwal

The TN-3 was made of a hollow cone nozzle ready to cover the surface of the spray completely. The control pots were sprayed with an aqueous mixture of the same technique. The largest application (corresponding to 4.48 kg / ha) in the test corresponds to the use of 50 mg of the test compound. The treated and control pots were placed in a greenhouse where the plants were grown for approx. they were exposed to light for 15 hours a day, and the temperature during the day was approx. ^B 23-29 C night was about 22 to 28 ^C, water and nutrients to the plants regularly, supplemental lighting (1 tos metal hslogenld lamps overhead) required received Szerman. Irrigation took place in excess. After 3 beta, the condition of the test plants, which showed oscillations and germs germinated and increased visualization of the untreated plants that emerged. A score of between zero and 100% means no damage, and 100% means complete eradication, with no germination. Table 3 illustrates the potency of the compounds of formula (I) in which the compounds of the present invention were used. spreadsheet

Pre-emergent effect

SXSffSS : -tesV ' ; ír.-ISIG BWC zs SVZ MQ SSÖd OL SWI c x s vn. WIV ZT 0902 LG C'íT MVE SS <? & <y FT i Ovolo GX 8W FIVE .......... C.03S SÜ 88 88 44 88 - neither 85 45 88 70 78 44 0.14 70 Ski 00 ? $ §8 ? s ? S 78 §0 '78 ? S 14? - - S - v 155 8/335 04 108 75 188 85 38 75 73 70 180 70 55 I AM? 0035 SS 98 75 100 §8 S8 78 Salt 85 78 59 188 0.14 73 SS 78 100 7.5 59 s $ e 55 38 55 80 50 190 - - - - - - 248 - - - - - i - i. · - : - i - : - 220 - - - - ·. 235 - ... - - : - < - : .1 i - : - - 23? .. - 7 -......... i V  - · : .. : .. - 2.0 - - - - - · - : - - : -

BWCKB = Xanthium strumarium BWMGL - ipomoea heöeracea

BWVEL ~ Abutllion íheophrasti} GW8LG ~ ragweed (Alopacurus rnyosproléesj GBCRB ~ Red-toed Muhar (Digitaria sanguinalis)

GWROX ~ Sorghum (Sorghum Bicolor)

BWLMQ ~ white libafopíChenepoPium album)

BWPIG ~ hairy porcupine amaranthue relrohsxus) BWWPT ~ dogwood milk (Euphorbla heterophyUs) G8WRN = common cockfoot (Echlnochloa crus-gali) GWGFT = giant muhar {Set

GWWOT - Wild oats (Village of Avena)

Claims (2)

1. A below (NI) -amide A <'u wherein A is O € _H2 GF _Ski OCH ₂ CHF ₂ OCH _{2 R} F CH _s, OEH ₂ CF ₂ OCH ₃ or GF (CH ₂ F) _2: B is CFs: and D is H. The compound of claim 1, wherein A is ΟΟΗ ₂ ΟΗΕ ₂ .